Porous composite particulate materials, methods of making and using same, and related apparatuses

ABSTRACT

In an embodiment, a porous composite particulate material includes a plurality of composite particles. Each composite particle includes an acid-base-resistant core particle at least partially surrounded by one or more layers of acid-base-resistant shell particles. The shell particles are adhered to the core particle by a polymeric layer. The shell particles and/or core particles may be made from an acid-base-resistant material that is stable in harsh chemical conditions. For example, the shell particles and/or core particles may be made from diamond, graphitic carbon, silicon carbide, boron nitride, tungsten carbide, combinations of the foregoing, or other acid-base-resistant materials. The porous composite particulate materials disclosed herein and related methods and devices may be used in separation technologies, including, but not limited to, chromatography, and solid phase extraction.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/052,185 filed on 10 May 2008, entitled “Synthesis of Porous DiamondParticles,” which is hereby incorporated herein, in its entirety, bythis reference.

BACKGROUND

Chromatography and solid-phase extraction (“SPE”) are commonly-usedseparation techniques employed in a variety of analytical chemistry andbiochemistry environments. Chromatography and SPE are often used forseparation, extraction, and analysis of various constituents, orfractions, of a sample of interest. Chromatography and SPE may also beused for the preparation, purification, concentration, and clean-up ofsamples.

Chromatography and SPE relate to any of a variety of techniques used toseparate complex mixtures based on differential affinities of componentsof a sample carried by a mobile phase with which the sample flows, and astationary phase through which the sample passes. Typically,chromatography and SPE involve the use of a stationary phase thatincludes an adsorbent packed into a cartridge or column. A commonly-usedstationary phase includes a silica-gel-based sorbent material. Mobilephases are often solvent-based liquids, although gas chromatographytypically employs a gaseous mobile phases. Liquid mobile phases may varysignificantly in their compositions depending on various characteristicsof the sample being analyzed and on the various components sought to beextracted and/or analyzed in the sample. For example, liquid mobilephases may vary significantly in pH and solvent properties.Additionally, liquid mobile phases may vary in their compositionsdepending on the characteristics of the stationary phase that is beingemployed. Often, several different mobile phases are employed during agiven chromatography or SPE procedure. Stationary phase materials mayalso exhibit poor stability characteristics in the presence of variousmobile phase compositions and/or complex mixtures for which separationis desired. The poor stability characteristics of stationary phasematerials in some mobile phases and complex mixtures, in some cases, mayeven preclude the possibility of using chromatography or SPE to performthe desired separation.

SUMMARY

Embodiments disclosed herein are directed to porous compositeparticulate materials, related methods of manufacture, and devices thatincorporate such porous composite particulate materials for use inseparation technologies, including, but not limited to, chromatographyand solid phase extraction. In an embodiment, a porous compositeparticulate material includes a plurality of composite particles. Eachcomposite particle includes an acid-base-resistant core particle atleast partially surrounded by one or more layers of acid-base-resistantshell particles. The shell particles may be bonded to the core particlesby a polymeric layer of one or more polymers. The shell particles and/orcore particles may be made from a material that is stable in harshchemical conditions. For example, the shell particles and/or coreparticles may be made from diamond, graphitic carbon, silicon carbide,boron nitride, tungsten carbide, combinations thereof, or other suitableacid-base-resistant material that is chemically stable in acids andbases over a wide pH range.

The one or more polymers used to adhere the shell particles to the coreparticles and/or to each other may also be selected to be stable inharsh chemical conditions. For example, in one embodiment, the one ormore adhering polymer may be an amine polymer. The one or more adheringpolymers may also be cross-linked (e.g., using epoxide moieties) to addmechanical strength to polymeric binding matrix and/or includefunctionalizing moieties (e.g., anionic moieties) to give the compositeparticulate material desired properties for separating components of amobile phase.

The shell particles may be bonded to the outside of the core particle toachieve a composite particle with a desired size and/or surface area.Moreover, the relative size of the core particles and shell particlesand the number of layers of shell particles may be selected to providecomposite particles with a surface area and porosity suitable forchromatography and/or solid phase extraction. The use of core particlesbonded to shell particles provides combinations of particle sizes andsurface areas that may not be possible with simple mixtures of un-bondedparticles of the same material.

In one embodiment, a method for manufacturing a porous compositeparticulate material includes providing a plurality ofacid-base-resistant core particles and a plurality ofacid-base-resistant shell particles. At least a portion of the coreparticles, at least a portion of the shell particles, or both may becoated with polymeric material. A portion of the shell particles areadhered to each core particle to form a plurality of compositeparticles. For example, each core particle may have a plurality of shellparticles bonded thereto by the polymer material.

In another embodiment, a separation apparatus for performingchromatography or solid phase separation is described. The separationapparatus includes a vessel having an inlet and an outlet. Any of theporous composite particulate materials disclosed herein may be disposedwithin the vessel. The vessel may be a column or a cassette suitable foruse in the fields of chromatography and/or solid phase separation (e.g.,high performance liquid chromatography (“HPLC”)).

The separation apparatus may be used to physically separate differentcomponents from one another. In one embodiment, a mobile phase includingat least two different components to be separated is caused to flowthrough the composite particulate material to physically separate the atleast two different components. At least one of the two differentcomponents is recovered.

In one embodiment, the composite particles are made from diamond,graphitic carbon, silicon carbide, boron nitride, tungsten carbide,combinations thereof, or other suitable acid-base-resistant materialthat is stable in chemically harsh conditions. The composite particlesin some cases may be used with a mobile phase that would typicallydegrade commonly used stationary phase materials, such as a silica gel.In the case where diamond particles are used as core particles and/orshell particles, the mobile phase may include organic solvents, whichare useful for separating lipids.

Features from any of the disclosed embodiments may be used incombination with one another, without limitation. In addition, otherfeatures and advantages of the present disclosure will become apparentto those of ordinary skill in the art through consideration of thefollowing detailed description and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate several embodiments of the invention, whereinidentical reference numerals refer to identical elements or features indifferent views or embodiments shown in the drawings.

FIG. 1 is a schematic flow diagram illustrating a method for making acomposite particulate material according to an embodiment;

FIG. 2 is a schematic diagram illustrating another method for making acomposite particulate material according to an embodiment;

FIG. 3 is a cross-sectional view of a vessel used for forming a body ofbonded composite particles according to an embodiment;

FIG. 4 is a cross-sectional view of a composite particle according to anembodiment;

FIG. 5 is a cross-sectional view an embodiment of a separation apparatusincluding a porous body comprising any of the porous compositeparticulate materials disclosed herein;

FIGS. 6A-6D are environmental scanning electron microscopy images ofdiamond particles with no shell diamond particles bonded thereto and thecomposite particles of Examples 6-8, respectively;

FIGS. 7A and 7B are environmental scanning electron microscopy images ofcomposite particles; and

FIGS. 8A-8C are graphs of area C—H stretch region, Brunauer Emmett andTeller surface-area measurements, and capacity as a function of numberof shell layers, respectively.

DETAILED DESCRIPTION I. Components Used To Make Porous CompositeParticulate Materials

A. Acid-Base-Resistant Particles

The porous composite particulate materials disclosed herein include aplurality of composite particles. Each composite particle includes anacid-base-resistant core particle, and a plurality ofacid-base-resistant shell particles that at least partially surround andare bonded to the core particle by a polymeric layer of polymer materialto impart a desired size and surface area. The core particles and shellparticles may be made from the same material or different materials. Thecore particles and/or shell particles may be of a solid, porous,composite, synthetic, and/or natural occurring material.

The core particles and the shell particles may have the same ordifferent particle sizes. As used herein, the phrase “particle size”means the approximate average particle size, such as average diameter orother average cross-sectional dimension of a plurality of particles,unless otherwise specified. In an embodiment, the shell particles aremuch smaller than the core particles to achieve a desiredcomposite-particle surface area. In an embodiment, the shell particleshave a particle size that is in a range from about 1 nm to 1000 nm, morespecifically in a range from about 2 nm to about 500 nm, even morespecifically in a range from about 5 nm to about 200 nm, and yet evenmore specifically in a range from about 10 nm to about 100 nm (e.g.,about 10 nm to about 20 nm). The core particles may have a particle sizein a range from about 1 μm to about 500 μm, more specifically about 1 μmto about 200 μm, or even more specifically in a range from about 1 μm toabout 100 μm. The desired particle size of the core particles may dependon the application in which the composite particle is to be used. In oneembodiment, the core particles have a particle size in a range fromabout 1 μm to 10 μm, more specifically about 1.5 μm to about 7 μm. Thisrange may be suitable for HPLC applications and the like. In anotherembodiment, the particle size of the core particles may be in a rangefrom about 5 μm to about 500 μm, or more specifically in a range fromabout 10 μm to about 150 μm. This larger range may be suitable for solidphase extraction applications and the like.

The acid-base-resistant shell and core particles may have a compositionthat is selected to be stable in sundry mobile phases, including organicsolvents, and chemically harsh acids and bases. Examples ofacid-base-resistant materials from which the shell particles and thecore particles may be made include, but are not limited to, diamond,graphitic carbon (e.g., graphite), silicon carbide, or another suitablematerial that is chemically stable in acids and bases over a pH range ofat least 3 to 12. For example, diamond, graphite, and silicon carbideare chemically stable in acids and bases over a pH range of about 0 toabout 14. Silica and alumina are examples of materials that are notacid-base-resistant materials, because they may significantly degrade inbases with a pH greater than 12. Other relatively acid-base-resistantmaterials include, but are not limited to, boron nitride and tungstencarbide.

Diamond possess remarkable chemical inertness, hardness, lowcompressibility, optical transparency, and high thermal conductivitythat may help eliminate thermal gradients in ultra performance liquidchromatography. Unlike silica, diamond does not easily dissolve inaqueous alkaline or acidic media, and it may be used in extremely harshchemical environments. These properties of diamond may be achieved withnaturally occurring diamond and/or synthetic diamond. Diamond materialmay also include other inorganic carbon materials, such as graphiticcarbon, fullerenes, combinations thereof, or other non-diamond carbon.

The acid-base-resistant shell and core particles may be produced throughany suitable method, including, for example, by forming carbonaceousmaterial into diamond material under ultra-high pressure andhigh-temperature conditions or other synthetic diamond particles.Additionally, the acid-base-resistant shell and core particles may bethe product of natural processes or by chemical vapor depositionprocesses. Acid-base-resistant shell and core particles may be producedby crushing and/or grinding a mineral starting material to obtain adesired sized particle. In an embodiment, the acid-base-resistant coreparticles may comprise micron-sized diamond particles with, for example,a particle size of about 1 μm to about 500 μm (e.g., about 1 μm to about100 μm) and the acid-base-resistant shell particles may comprise diamondparticles, with for example, a particle size of about 1 nm to 1000 nm(e.g., about 2 nm to about 200 nm). The acid-base-resistant shell andcore particles may have a spherical shape, a faceted shape, an irregularshape, or other suitable geometry.

B. Polymeric Materials

The coating or binding polymer used to bond to the shell particles tothe core particle and/or other shell particles may be any polymericmaterial that may be applied in a coating to adhere theacid-base-resistant particles to one another. For example, the polymercoating may include a polymeric material comprising one or more polymersthat provide the porous composite particulate material desiredproperties for separating components of a mobile phase. The polymercoating may include macromonomers, oligomers, and/or various polymers,without limitation. The polymer coating may include combinations and/ormixtures of different polymeric materials and/or used to form differentlayers of polymers as described more fully below.

In one embodiment, the polymer coating or binding polymer may include atleast one amine group. The amine polymer may be selected to bechemically stable in many of the same mobile phases that diamondparticles or other acid-base-resistant materials disclosed herein arestable. In an embodiment, the amine polymer includes at least onependant amine group and/or at least one primary, secondary, tertiary,and/or quaternary amine group. In various embodiments, the polymercoating may include for example, polyallylamine, polyethylenimine,polylysine, polyvinylamine, chitosan, trimethylchitosan (i.e.,quaternized chitosan), polydiallydimethyl ammonium chloride (“PDADMAC”),poly(N,N′-dimethylaminoethylmethacrylate), poly(2-vinylpyridine),poly(4-vinylpyridine), polyvinylimidazole, poly(2-(dimethylamino)ethylacrylate), and/or poly(2-aminoethyl methacrylate) hydrochloride,combinations of the foregoing, and/or derivatives of the foregoing.

Polyethylenimine may be present in the polymer coating in a wide rangeof molecular weights and degrees of branching. Chitosan may be producedby the deacetylation of chitin, and chitin may be deacetylated tovarious degrees. Polymers in the coating may be substantially linear orat least partially branched. Polymers including amines therein may beprotonated, deprotonated, or partially protonated prior to, during,and/or following deposition on a surface. Additionally, the polymercoating may comprise any suitable naturally occurring proteins and/orpeptides.

In additional embodiments, the polymer coating may include a homopolymerand/or a copolymer compound formed from monomer subunits including, forexample, allylamine, vinylamine, ethylenimine, vinyl amine, lysine,arginine, histidine, 2-isocyanatoethyl methacrylate, aziridine,1-vinylimidazole, 1-vinyl-2-pyrrolidone, 2-vinylpyridine,4-vinylpyridine, 2-(dimethylamino)ethyl acrylate, 2-aminoethylmethacrylate hydrochloride, and/or 2-(tert-butylamino)ethylmethacrylate.

Additionally, the polymer coating may include any suitable monomers thatmay be converted into amines after polymerization by deprotection,hydrolysis, and/or by simple chemical transformation. In variousembodiments, the polymer coating may include monomers based onoxazoline, which may be polymerized to form polyoxazolines and/or whichmay then be hydrolyzed. Amine-comprising monomers forming a polymericcompound in coating may be protonated, deprotonated, or partiallyprotonated prior to, during, and/or following polymerization.

In at least one embodiment, monomers forming a polymer in the polymercoating may be interspersed with other monomer units such as2-hydroxyethylacrylate, styrene, 1,3-butadiene, methyl methacrylate,methyl acrylate, butyl acrylate, dodecyl methacrylate, acrylonitrile,acrylic acid, methacrylic acid, 4-vinylbenzyl chloride,4-(trifluoromethyl)styrene, 3-nitrostyrene, vinyl ether, or vinylacetate.

The polymer coating may include a polymeric compound having variouschain lengths and various degrees of branching. For example, thepolymeric coating may include a polymeric compound having aweight-average molecular weight or number-average molecular weightranging from about 1,000 to about 2,500,000. In certain embodiments, thepolymer coating may include a polymeric compound having a weight-averagemolecular weight or number-average molecular weight ranging from about5,000 to about 100,000. Additionally, the polymer coating may include apolymeric compound having a weight-average molecular weight ornumber-average molecular weight ranging from about 30,000 to about60,000 monomer units. In additional embodiments, the polymer coating mayinclude polymeric compounds having a weight-average molecular weight ornumber-average molecular weight of less than about 1,000. The polymercoating may optionally include oligomers having a chain length of from 2to 100 monomer units in length. As used herein, the term “polymericcompound” includes oligomers as well as polymers of varying chainlengths and molecular weights, unless otherwise specified.

Additional information about suitable polymers for use in the porouscomposite particulate materials disclosed herein may also be found inU.S. patent application Ser. No. 12/039,382 filed on 28 Feb. 2008,entitled “Methods For Direct Attachment Of Polymers To Diamond SurfacesAnd Articles Formed Thereby,” naming Matthew R. Linford and Li Yang asinventors, which is hereby incorporated herein, in its entirety, byreference.

In some embodiments, the polymer coating includes one or more anionicpolymers. Anionic polymers may be useful for ion exchangechromatography. Example of suitable anionic polymers include, but arenot limited to poly(styrenesulfonic acid, sodium salt), poly(acrylicacid), poly(methacrylic acid), derivatives of these, and/or combinationsof these. While the polymer coating may be suitable for separatingcomponents of a mobile phase, uncoated, exposed surfaces of the coreparticles and/or shell particles (e.g., diamond core and shellparticles) may be functionalized for separating components of a mobilephase as an alternative to or in addition to using the polymer coating.

II. Methods for Making Porous Composite Particulate Materials

Reference is now made to FIG. 1 which illustrates a schematic flowdiagram 100 of an embodiment of a method for making a porous compositeparticulate material from core particles, shell particles, and polymermaterial. FIG. 1 is a schematic illustration and does not necessarilyrepresent the actual shape or sizes of the acid-base-resistant coreparticles and/or acid-base-resistant shell particles. Moreover, FIG. 1illustrates a method for forming a single composite particle, and theporous composite particulate materials disclosed herein include aplurality of such composite particles.

In step 110, a plurality of acid-base-resistant core particles 114 areimmersed in a polymeric material that coats and at least partiallysurrounds each core particle 114 with a respective polymer coating 112.In step 120, a first portion of acid-base-resistant shell particles areadhered to each core particle 114 to form a first porous shell layer 116of shell particles. The shell particles adhere to the core particles 114via the polymer coating 112. The thickness and composition of polymercoating 112 may be any thickness that is sufficient so that the shellparticles adhere to the core particles 114. The thickness of the polymercoating 112 is typically sufficiently sized so that the polymer does notfill all the voids between adjacent shell particles of the first porousshell layer 116. Maintaining a relatively thin coating may help toprovide a desired surface area. In one embodiment, the thickness of thepolymer coating 112 may be in a range from about 1 nm to about 1 μmthick, and more specifically in a range from about 5 nm to about 100 nm.In an embodiment, the thickness of the polymer coating is less than theaverage diameter of the shell particles, more specifically the thicknessis less than about half the diameter of the shell particles, and evenmore specifically less than one-fourth the diameter of the shellparticles. The polymer coating 112 may be cured or otherwise chemicallymodified in step 120 or in subsequent steps, as described more fullybelow.

The portion of shell particles may be applied to each core particle 114by suspending the shell particles in a solvent and immersing the coatedcore particles 114 in the suspension of shell particles or,alternatively, the suspension of shell particles may be caused to flowover the core particles 114. Any solvent suitable for suspending thecore particles and/or the shell particles may be used. In oneembodiment, the core particles and/or the shell particles may besuspended in water. The coating of shell particles on the coated coreparticles 114 yields intermediate composite particles 128 having roughsurfaces. The rough surface includes voids (i.e., recesses in thesurface) between the individual shell particles of the first porousshell layer 116.

A plurality of the intermediate composite particles 128 may be used as afinal product if desired and/or cross-linked to improve mechanicalstability. However, substantially increased surface area may be achievedby repeating steps 110 and 120 to yield intermediate composite particleswith increasing numbers of porous shell layers. As shown in step 130, apolymer coating 113 may be applied to the surface of the intermediatecomposite particle 128 to coat the shell particles of the first porousshell layer 116. The polymer coating 113 may be made from the same or adifferent polymeric material than the polymeric coating 112 used in step110. The thickness of the polymer coating 113 is typically sufficientlysized so that the polymer does not fill all the voids between adjacentshell particles of the first porous shell layer 116. In step 140, asecond portion of the shell particles may be applied to intermediatecomposite particle 138 to yield second intermediate composite particles142 each having a second porous shell layer 144 of shell particlesbonded to the first porous shell layer 116.

In step 150, yet a third polymer coating 115 may be coated onintermediate composite particle 144 to yield intermediate particles 152,with the shell particles of the second porous shell layer 144 beingcoated. The polymer coating 115 may be made from the same or a differentpolymeric material than the polymeric coatings 112 or 113 used in steps110 or 130. The thickness of the polymer coating 115 is typicallysufficiently sized so that the polymer does not fill all the voidsbetween adjacent shell particles of the second porous shell layer 144.In step 160, a third portion of shell particles may be adhered to thesecond porous shell layer 144 of intermediate particles 152 to yieldintermediate composite particles 164 having a third porous shell layer162 of shell particles.

The porous shell layers 116, 144, and 162 may have differently orsimilarly sized shell particles. Also, the shell particles in thedifferent layers may have a different composition and/or be bonded usingdifferent compositions of polymer. The different shell particles, coreparticles, and polymers may be selected from any combination of thecomponents described herein or components known in the art that aresimilar and/or provide similar function.

The method of adding additional porous shell layers may be continueduntil a desired number of porous shell layers and/or a desired surfacearea is achieved for the composite particles. In one embodiment, themethod of forming porous shell layers may be repeated at least 5 times,more specifically at least about 10 times, or even more specifically atleast 20 times to yield composite particles having 5, 10, or 20 porousshell layers, respectively. This method continues until the desirednumber of porous shell layers is achieved. In one embodiment, the numberof porous shell layers is at least about 3, more specifically at leastabout 5, even more specifically at least about 10, yet even morespecifically at least 20, and most specifically at least 50.

The shell particles, core particles, and/or composite particles may eachbe completely or partially coated with the polymer coating. In manycases, the polymer coating is applied using immersion, which tends toapply a relatively even coating around an entire particle. However, insome embodiments, one or more of the acid-base-resistant particles mayonly be partially coated with a sufficient polymer coating to adhere toother particles. In addition, the application of the shell particles maybe asymmetric so as to create asymmetric composite particles.

Once the polymer has been attached to the surface of the core particles,there are numerous chemical reactions that may be performed, includingcross-linking and curing. The cross-linking and/or curing may be carriedout separately at any of the steps described in method 100. In oneembodiment, curing may be performed for each step that results in theformation of a porous shell layer. In one embodiment, cross-linking iscarried out as a final step 170. However, the step 170 is optional andembodiments also include the use of polymers that do not require curingand/or cross-linking.

In embodiments where curing and/or cross-linking is performed, thepolymer coating may be cured and/or cross linked using any suitabletechnique such as thermal curing and/or radiation curing such as curingusing infrared or ultraviolet curing lights. Curing may increase thephysical and/or chemical stability of the polymer coating. For example,curing may increase the stability of the polymer coating when exposed toharsh conditions, such as high and/or low pH solutions, which may allowa stationary phase including the porous composite particulate materialto be cleaned and/or otherwise used under harsh conditions. Some porouscomposite particulate materials described herein may be used incombination with strong solvents, high pH conditions, and/or low pHconditions. The ability to clean a column under harsh conditions mayenable reuse of a previously contaminated stationary phase. In at leastone embodiment, curing may cause amide linkage to form between variouscompounds in the polymer coating. Additionally, curing may cause amideor other linkages to form between various compounds in the polymercoating and the surface of the acid-base-resistant particles.

In additional embodiments, a polymer in the coating may be allowed toreact with another compound in the coating before, during, and/or afterdepositing the coating on the acid-base-resistant particles to increasethe molecular weight of the coating. Increasing the molecular weight ofthe polymer may be advantageous in that the higher molecular weightcoating may have increased stability in a variety of conditions.

In additional embodiments, the coating and/or at least a polymericcompound forming the coating may be cross-linked during a curingprocess, such as a thermal and/or pressure-induced curing process, asdescribed above. Additionally, the curing of the coating and/or at leasta polymeric compound forming the coating, may be cross linked byexposing the coating to radiation. Cross-linking may cause stable bondsto form with amine groups and/or other chemical moieties in a polymericcompound in the coating, thereby increasing the stability of coating.Additionally, cross-linking compounds in the coating using compoundshaving epoxy groups may produce hydroxyl groups in and/or on thecoating, resulting in a change in chemical characteristics of thecoating and providing potential reactive sites on the coating.

In certain embodiments, a cross-linking agent having at least twofunctional bonding sites may be used to effect cross-linking of at leasta portion of the coating and/or at least a polymeric compound formingthe coating. For example, a cross-linking agent may comprise a diepoxidecompound having at least two epoxide groups, each of which may bond withan amine group. A cross-linking agent having at least two functionalbonding sites may bond with at least one amine group on at least two ormore polymeric molecules and/or compounds. In an additional embodiment,a cross-linking agent having at least two functional bonding sites maybond with at least one amine group on at least two separate sites on asingle polymeric molecule. Additionally, a cross-linking agent having atleast two functional bonding sites may bind to a polymeric compoundforming the coating at only one of the at least two functional bindingsites.

Examples of cross-linking agents suitable for cross-linking the polymercoating and/or at least a polymeric compound forming the polymer coatingmay include any type of compound containing two or more amine reactivefunctional groups, including, for example, diisocyanates,diisothiocyanates, dihalides, diglycidyl ethers, diepoxides,dianhydrides, dialdehydes, diacrylates, dimethacrylates, dimethylesters,di- and/or triacrylates, di- and/or trimethacrylates, and/or otherdiesters. In at least one embodiment, acrylates and/or methacrylates mayreact with an amine by Michael addition.

In addition, suitable cross-linking agents may include, withoutlimitation, 1,2,5,6-diepoxycyclooctane, phenylenediisothiocyanate,1,4-diisocyanatobutane, 1,3-phenylene diisocyanate,1,6-diisocyanatohexane, isophorone diisocyanate, diethylene glycoldiglycidyl ether, 1,4-butanediol diglycidyl ether, bisphenol Adiglycidyl ether, poly(ethylene glycol) diglycidyl ether, poly(propyleneglycol) diglycidyl ether, octanedioic acid dichloride (suberic aciddichloride), phthaloyl dichloride, pyromellitic dianhydride,1,3-butadiene diepoxide, p-phenylene diisothiocyanate,1,4-dibromobutane, 1,6-diiodohexane, glutaraldehyde, 1,3-butanedioldiacrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate,dipentaerythritol pentaacrylate, 1,6-hexanediol dimethacrylate, and/orpropoxylated (3) glyceryl triacrylate. Cross-linking agents mayadditionally comprise at least one functional group suitable for bondingwith non-amine functional groups that may be present on polymers in thecoating disclosed herein.

In at least one embodiment, an epoxide compound such as,1,2,5,6-diepoxycyclooctane, may have at least one highly strainedepoxide ring that may be reactive with various amine groups in thepolymer coating. Various alcohols may be used as effective solvents foramine-epoxide reactions. Reaction of the at least one highly strainedepoxide ring with an amine group in the coating may result inimmobilization of hydrophobic cyclooctyl rings and hydrophilic hydroxylgroups in the coating, leading to the formation of a mixed-modestationary phase in the coating. This type of mixed-mode stationaryphase may be employed for various uses, including, for example,retention of proteins and small molecules such as drugs under reversephase and/or normal conditions in an SPE column.

The amine group is an extremely versatile chemical reagent with a richchemistry. Information about some of these reactions may be found inU.S. patent application Ser. No. 12/040,638 filed on 29 Feb. 2008,entitled, “Functionalized Diamond Particles And Methods For PreparingThe Same,” naming Matthew R. Linford and Gauray Saini as inventors,which is hereby incorporated herein, in its entirety, by this reference.

FIG. 2 describes another embodiment of a method 200 in which all or aportion of the acid-base-resistant shell particles are coated withpolymer material prior to being adhered to the core particles or to eachother (e.g., in a layer-by-layer process described above). In method200, step 210 includes applying a polymer coating to acid-base-resistantshell particles to yield coated particles 214. In step 220,acid-base-resistant core particles 222 are mixed with the shellparticles 212 using any suitable mixing process. The polymer coating onthe coated shell particles 214 bonds the shell particles 212 to the coreparticles 222 to yield an intermediate composite particle 224.Additional layers of shell particles may be bonded to intermediatecomposite particle 224 by adding a second portion of coated shellparticles 214 or alternatively by coating the composite particles 224with polymer material and shell particles as described in steps 110 and120. The method 200 may also include additional curing and/orcross-linking steps as described above with regard to the method 100.

In one embodiment, the porous composite particulate material may includea body of bonded composite particles. The body may be formed by forminga bed of coated intermediate composite particles (e.g., compositeparticles 224) and polymerizing or otherwise joining the individualcomposite particles together to form a coherent body. Forming a body ofbonded composite particles may allow the individual particles tomaintain their integrity.

In other embodiments, some of the core particles may be coated withpolymer material and some of the core particles may be uncoated. Alsosome of the shell particles may be coated with polymer material and someof the shell particles may be uncoated. In such an embodiment, thecoated/uncoated core particles may be mixed together with thecoated/uncoated shell particles to form a plurality of compositeparticles.

FIG. 3 describes a method for forming a body of bonded compositeparticles in vessel according to another embodiment. In this embodiment,a vessel 302 is provided that includes an inlet 304 and an outlet 306. Aplurality of core particles are positioned within the vessel 302 to forma particle bed 308. The core particles may be retained in the vessel bya frit 310. In a first step, the vessel 302 is at least partially filledto form the bed 308. In a second step, the particles in the bed 308 areat least partially coated with a layer of polymer. In a third step, asuspension of shell particles is caused to flow through the bed 308,such as through voids between adjacent core particles. The shellparticles bond to the core particles through the layer of polymer.Additional porous shell layers may be added as described above withregard to FIGS. 1 and 2. The body may be formed by curing and/orcross-linking the intermediate composite particles so-formed whilepacked in the vessel as a bed. The bonded composite particles haveimproved structural integrity, which may help prevent shell particlesfrom being freed during use of the porous composite particulate materialin chromatography.

III. Porous Composite Particulate Materials

The porous composite particulate materials described herein providedesired sizes, porosity, surface areas, and chemical stability suitablefor chromatography and SPE techniques. When used in chromatography andSPE, high-resolution separation may be achieved with relatively low backpressure, which is in contrast to columns and cassettes that use highsurface area particles without the composite structure described herein.

The porous composite particulate materials include a plurality ofcomposite particles, with each composite particle including a coreparticle at least partially surrounded by one or more layers of shellparticles. The shell particles are bonded to the core particles by apolymer coating. The shell particles and/or core particles may be madefrom the acid-base-resistant materials described above, including butnot limited to diamond particles, graphitic carbon, silicon carbide,boron nitride, tungsten carbide, and combinations thereof. The porouscomposite particulate material may also have any combination of polymersdescribed above. However, in an embodiment, the polymer coating thatbonds the core particles to the shell particles and/or the shellparticles to themselves is an amine polymer.

The composite particles may be provided in the form of finely divideddiscrete particles (e.g., a powder). Alternatively, the compositeparticles may be provided as a body of bonded composite particles. Whenthe composite particles are provides as a body of bonded compositeparticles, the body may exhibit dimensions suitable for use in aseparation apparatus, such as, but not limited to, separation devicesused in HPLC.

In one embodiment, the composite particles have a particle size in arange from about 1 μm to 500 μm, more specifically about 1 μm to 200 μm,or even more specifically in a range from about 1 μm to about 150 μm. Inone embodiment, the composite particles have a particle size in a rangefrom about 1 μm to about 10 μm, or more specifically about 1.5 μm toabout 7 μm. This particle range may be particularly useful for HPLCapplications and the like. In another embodiment, the compositeparticles can have a particle size can be in a range from about 5 μm toabout 500 μm, or more specifically in a range from about 10 μm to about150 μm. This larger particle range may be more suitable for use in solidphase extraction applications and the like.

The composite particles may include a desired surface area. The surfacearea may depend on core and shell particle size, number of porous shelllayers, and particle geometry. However, the surface area of thecomposite particles is higher than a similarly sized core particle dueto the additional surface area provided by the shell particles. In anembodiment, the surface area may be measured using the Brunauer Emmettand Teller (“BET”) technique and is in a range from 1-500 m²/g forcomposite particles having a particle size in a range from about 1 μm to500 μm, more specifically in a range from 25-300 m²/g, or even morespecifically 50-200 m²/g. In one embodiment, the composite particleshave a particle size in a range from about 1 μm to 10 μm may have asurface area in a range from about 10-500 m²/g, more specifically in arange from 25-200 m²/g, and even more specifically in a range from 25-60m²/g. In another embodiment, composite particles having a particle sizefrom about 10 μm to 150 μm may have a surface area in a range from about5-200 m²/g, or more specifically 10-100 m²/g. In yet another embodiment,composite particles having a particle size in a range from about 250 μmto about 500 μm may have a surface area at least about 5 m²/g, and evenmore specifically at least about 10 m²/g for composite particles with aparticle size in a range from about 250 μm to about 500 μm.

In a more detailed embodiment, a composite particle including a diamondcore particle having a size of about 2.5 μm to about 5 μm and 1-50porous shell layers of diamond shell particles having a particle size ofabout 5 nm to about 50 nm may have a surface area of about 1 m²/g toabout 60 m²/g. In a more specific embodiment, a composite particleincluding a diamond core particle having a size of about 2.5 μm and10-50 porous shell layers of diamond shell particles having a particlesize of about 5 nm to about 10 nm may have a surface area of about 14m²/g to about 60 m²/g. In another more specific embodiment, a compositeparticle including a diamond core particle having a size of about 5 μmand 10-50 porous shell layers of diamond shell particles having aparticle size of about 5 nm to about 10 nm may have a surface area ofabout 7 m²/g to about 33 m²/g.

FIG. 4 illustrates a composite particle that includes at least a bilayerof polymer according to another embodiment. A bilayer of polymer may beconstructed from a first polymer coating 402 on an acid-base-resistantcore particle 404. The polymer coating 402 may be formed using steps 110and 120 as described above. A bilayer is formed by adding a functionalpolymer layer 406 and a second polymer coating layer 408. The polymerlayers 402 and 408 are binding layers selected for bonding the shellparticles to the core particles and/or the shell particles to the shellparticles. The functional layer 406 is a polymeric layer that imparts adesired functionality to the composite particle. The polymers that areused to make the functional layer 406 may be selected from the polymersmentioned above that are useful for forming layers 402 and 408. However,the formation of a bilayer allows the selection of two or more differentpolymers to form the composite thereby allowing the different polymerlayers to be optimized for different purposes. Typically, the layers 402and 408 are selected for bonding inorganic polymers together and thefunctional polymer layer 406 is selected for providing a separatefunction such as, but not limited to properties related to separationefficiency. In one embodiment, the functional polymer layer 406 may bean anionic polymer.

In some embodiments, an additional particulate component may be embeddedin the porous shell layers of the shell particles. The additionalparticulate component may be any organic or inorganic material thatprovides a desired property to the porous composite particulatematerial. In one embodiment, the additional component may be initiallyincluded in the manufacture of the composite particles but then removed.For example, the porous shell layers may include silica particles thatexhibit a selectivity to be removed over more acid-base-resistantparticles, such as diamond, graphite, or boron nitride shell particles.This method may allow a composite particle to be formed with particularstructural features. Alternatively, the additional component may beincluded with the purpose of removing or eluding out the componentduring use. For example, the additional component may be configured toelute out over time in the presence of a mobile phase.

In one embodiment, the additional component may be a particle that hasaffinity for a drug or other chemical reagent. In one embodiment, theadditional component may include a catalytic reagent. The additionalcomponent may be included in the core particles and/or the layers ofshell particles.

IV. Separation Apparatuses and Methods

FIG. 5 is a cross-sectional view of a separation apparatus 500 accordingto an embodiment. The separation apparatus 500 may include a column 502defining a reservoir 504. A porous body 506 (e.g., a porous compositebed, porous disk, other porous mass, etc.) may be disposed within atleast a portion of the reservoir 504 of the column 502. The porous body506 may comprise any of the porous composite particulate materialsdisclosed herein in bonded or powder form. The porous body 506 is porousso that a mobile phase may flow therethrough. In various embodiments, afrit 508 and/or a frit 510 may be disposed in column 502 on either sideof porous body 506. The frits 508 and 510 may comprise any suitablematerial that allows passage of a mobile phase and any solutes presentin the mobile phase, while preventing passage of the compositeparticulate material present in porous body 506. Examples of materialsused to form the frits 508 and 510 include, without limitation, glass,polypropylene, polyethylene, stainless steel, and/orpolytetrafluoroethylene.

The column 502 may comprise any type of column or other device suitablefor use in separation processes such as chromatography and solid phaseextraction processes. Examples of the column 502 include, withoutlimitation, chromatographic and solid phase extraction columns, tubes,syringes, cartridges (e.g., in-line cartridges), and plate containingmultiple extraction wells (e.g., 96-well plates). The reservoir 504 maybe defined within an interior portion of the column 502. The reservoir504 may permit passage of various materials, including various solutionsand solvents used in chromatographic and solid-phase extractionprocesses.

The porous body 506 may be disposed within at least a portion ofreservoir 504 of the column 502 so that various solutions and solventsintroduced into the column 502 to contact at least a portion of theporous body 506. The porous body 506 may comprise a plurality ofsubstantially non-porous particles in addition to the composite porousmaterial.

In certain embodiments, frits, such as glass frits, may be positionedwithin the reservoir 504 to hold porous body 506 in place, whileallowing passage of various materials such as solutions and solvents. Insome embodiments, a frit may not be necessary, such as the body ofbonded-together composite particles as described above with reference toFIG. 4.

In one embodiment, the separation apparatus 500 is used to separate twoor more components in a mobile phase by causing the mobile phase to flowthrough the porous body 506. The mobile phase is introduced through aninlet and cause to flow through the porous body 506 and the separatedcomponents may be recovered from the outlet 512.

In one embodiment, the mobile phase includes concentrated organicsolvents, acids, or bases. In one embodiment, the mobile phase includesa concentrated acid with a pH less than about 3, more specifically lessthan about 2. In another embodiment, the mobile phase includes a basewith a pH greater than about 10, more specifically greater than about12, and even more particularly greater than 13.

In one embodiment, the separation apparatus 500 is washed between aplurality of different runs where samples of mixed components areseparated. In one embodiment, the washing may be performed with water.In another embodiment, a harsh cleaning solvent is used. In thisembodiment, the harsh cleaning solvent may be a concentrated organicsolvent and/or a strong acid or base. In one embodiment, the cleaningsolvent has a pH less than about 3, more specifically less than about 2.In another embodiment, the cleaning solvent has a pH greater than about10, more specifically greater than about 12, and even more particularlygreater than 13.

V. Examples

The following examples are for illustrative purposes only and are notmeant to be limiting with regards to the scope of the specification orthe appended claims. For example, the present disclosure and claims arenot limited to the use of diamond particles, unless otherwise specified.

Example 1 Synthesis of Composite Diamond Particles

Example 1 describes the synthesis of core-shell composite particlesusing an amine polymer, micron-sized core diamond particles, andnano-sized shell diamond particles.

The following reagents were provided: Poly(allylamine) (Mw ca. 65,000,20 wt. % solution in water, Aldrich, Milwaukee, Wis.), polyethylenimine(Mw 25,000, Aldrich, Milwaukee, Wis.) (1,2,5,6-diepoxycyclooctane (96%,Aldrich) and 1,16-hexadecanedioic acid (>98%, Aldrich) were used asreceived. Diamond powders (50-70 μm and 100-250 nm) were provided byU.S. Synthetic Corporation of Orem, Utah.

Core-shell particles were synthesized from 50-70 μm core particles and100-250 nm shell diamond particles. The microdiamond core particles werecleaned in piranha solution (70% H₂SO₄:30% conc. H₂O₂) at 100° C. for 1h.

The piranha cleaned diamonds were then sonicated in ultrapure water, andwashed extensively with ultrapure water on a filter funnel. Thenanodiamond shell particles were not cleaned in piranha solution, butused as received.

Core-shell composite particles containing 0-5 and 9 bilayers ofPAAm-nanodiamond were synthesized. A 0.25 wt. % solution ofpoly(allylamine) was made from 1.55 g of PAAm (20 wt. % solution inwater) in 125 mL of ultrapure water, and 12 g of piranha-cleanedmicrodiamond powder were poured into this solution. The solution wasshaken for ca. 10 s every 10 min for 1 h to expose the particles toPAAm. After immersion in the PAAm solution, the microdiamond powder waswashed extensively with ultrapure water in a filter funnel. An aqueoussuspension of nanodiamond powder was prepared by sonicating 1 g ofnanodiamond shell particles in 120 mL of ultrapure water, and 12 g ofPAAm-functionalized microdiamond powder was poured into this suspensionfor 1 h. This suspension of nanodiamond and PAAm-functionalized diamondwas shaken gently for ca. 10 s every 10 min to expose all surfaces ofthe PAAm-functionalized microdiamond particles to nanodiamond particles(i.e., shell particles). After adsorption, the aqueous suspension wasfiltered on a medium pore size (25 μm-50 μm) filter funnel. As the sizeof the nanodiamond particles is much smaller than the pore size of thefilter funnel, unbounded nanodiamond particles in the suspension easilypass through the pores of the filter funnel leaving behind microdiamondscontaining one layer of adsorbed nanodiamond particles. These particleswere washed extensively with ultrapure water on the filter funnel toremove any non-adsorbed nanodiamonds. Approximately 2.8 g of core-shellcomposite particles (having microdiamonds containing one layer ofadsorbed nanodiamond particles) were taken from this lot forcharacterization.

Examples 2-4 Synthesis of Multi-Layered Diamond Composite Particles

The remaining composite particles from Example 1 were used as anintermediate composite particle to make composite particles having aplurality of layers of shell particles. The intermediate compositeparticles were poured into the aqueous solution of PAAm described inExample 1. The intermediate composite particles were held for 1 h toamine functionalize the outer surface of the first layer of shellparticles. Treatment with the PAAm solution and the cleaning procedurewere repeated as in Example 1 (vide supra). A powder was recovered andpoured into an aqueous suspension of nanodiamonds. The depositionconditions were as for the earlier layer (vide supra). Another 2.8 g ofthis functionalized diamond powder were taken, and the remaining diamondpowder was treated in the same way. This procedure of immersion in theaqueous solution of PAAm followed by immersion in the aqueous suspensionof nanodiamond was performed 3, 5, and 9 times to achieve a compositeparticle with the desired number of layers of nanodiamond particles forExamples, 2-4, respectively. A flow diagram of the synthesis of thecomposite particles of Examples 2-4 is illustrated in FIG. 1, where thepolymer coating used is PAAm and the acid-base-resistant particles coreparticles and acid-base-resistant shell particles each include diamond.

Example 5 Synthesis of Bonded Diamond Composite Particles

Example 5 describes the synthesis of core-shell composite particles thatare bonded together. Bonded core-shell composite particles have beenfound to be particularly useful in HPLC. Core-shell particles wereprepared from 5 μm and 10-50 nm diamond particles. Nanodiamond particleswere used as their aqueous suspension (8.17 wt. %), which had asurfactant in it. The addition of surfactant prevented the agglomerationof nanodiamond particles. Unlike the preparation for core-shellcomposite particles for SPE (i.e., described in Example 1), theparticles in Example 5 were prepared in a test tube. Approximately 1.6 gof 5 μm diamond powder was poured into ca. 30 ml water in a test tube. A1.33 wt. % solution of polyethylenimine (“PEI”) was made in water, and400 μl of this solution was added into the test tube. The test tube wasshaken vigorously for 3 min to expose diamond particles to the polymer.After treatment with PEI solution, the solution was centrifuged for 1min at 5000 rpm. As a result of that the centrifuging, diamond particlessettled down at the bottom of the test tube. The supernatant wasdiscarded, and more water was added to the test tube. The test tube wasshaken vigorously to remove non-specifically adsorbed polymer from thesurface, and centrifuged afterwards. This cleaning procedure wasrepeated two $times. After cleaning, 400 μl of nanodiamond suspensionwas added to 30 ml suspension of PEI coated 5 μm diamond particles inthe test tube, and the test tube was shaken vigorously for 3 minutes.After treatment with nanodiamond particles, the microdiamond particleswere washed with copious amounts of water using the same procedure asfor PEI treated particles mentioned before. The alternate treatment withPEI and nanodiamond was continued until 20 bilayers of nanodiamond andPEI were formed on the surface of the 5 μm diamond particles.

Examples 6-9 Chemical Cross-Linking of Composite Particles

Examples 6-9 describes a method of improving the mechanical stability ofcore-shell composite particles by cross-linking the polymer of adjacentparticles. Nanodiamond particles, microdiamond particles and adsorbedPAAm are attached to themselves through relatively weak non-covalentinteractions. The mechanical stability of these particles was improvedby chemical cross-linking with 1,2,5,6-diepoxycyclooctane.

In Examples 6-8, chemical cross-linking was carried out on the compositeparticles of Examples 2-4 respectively. The cross-linking was carriedout as a final step in the synthesis of the core-shell particles. Ineach of Examples 6-8, a 2.3 wt. % solution of 1,2,5,6-diepoxycyclooctane(made by dissolving 0.1747 g in 7.5 mL isopropanol) was used tochemically cross-link the PAAm-nanodiamond of the core-shell compositeparticles of Examples 1-4, respectively. Approximately 2.6 g of eachdifferent core-shell particle was used for chemical cross-linking. Thereaction was done in a sealed thick-walled glass tube at 80° C.overnight. After the reaction, the core-shell diamond powder was washedextensively in the filter funnel with copious amounts of isopropanolfollowed by dichloromethane.

FTIR based surface analysis of Examples 6-8 was performed with aMagna-IR 560 spectrometer from Nicolet (Madison, Wis.). Environmentalscanning electron microscopy (“ESEM”) images of the samples wereacquired using a FEI (Philips) XL30 ESEM FEG instrument. Since diamondis an insulator, the diamond powder was adhered to a conductive, doublestick carbon tape, and the instrument was operated in low-vacuum mode toprevent the charging of the surface. Samples were sent to Micromeritics(Norcross, Ga.) for BET surface area and pore size analysis.

The layer-by-layer deposition of nanodiamond particles around a solidmicrodiamond core was monitored by four techniques: diffuse reflectantinfrared Fourier transform (“DRIFT”), ESEM, BET surface-areameasurements, and sorbent (analyte) capacity measurements.

Referring to FIGS. 6A-6B, ESEM images of a control sample and Examples6-8 are shown. Images of Examples 6-8 are shown in FIGS. 6B-6D,respectively. The images in FIG. 6A shows core diamond particles with noshell diamond particles (i.e. control particles). It is clear from theESEM images that PAAm-functionalized, nanodiamond particles startadsorbing on the surface of microdiamonds after their first immersion inaqueous suspension of nanodiamonds. It is observed that with an increasein the number of nanodiamond layers, the surface becomes fuzzier inappearance. FIG. 7A shows an ESEM image of a core diamond having noshell diamonds and FIG. 7B shows an ESEM image of 5 μm diamond particlesthat have 20 bilayers of PEI nanodiamond. The high surface area isclearly identifiable by the fuzzy texture on the particle surface forthe particles with 20 bilayers.

Core-shell composite particles were also characterized according totheir number of shell layers. FIGS. 8A-8C are plots of the area C—Hstretch region, the BET surface area (m²/g), and sorbent capacity (mg/g)for a given number of shell layers, respectively. Referring to FIG. 8A,DRIFT was used to measure the area of the C—H stretching region of thecore-shell composite particles as a function of the number ofPAAm-nanodiamond bilayers. It is evident that the area of the C—Hstretching region increases with an increase in the number ofPAAm-nanodiamond bilayers. Clearly, with an increase in the number ofnanodiamond layers, the amount of the adsorbed polymer also increases,which leads to an increase in the number of CH₂ groups, and IRadsorption.

Referring to FIG. 8B, one important feature is the increase in surfacearea that may be achieved with increasing number of layers. The plot ofthe BET surface area of the composite particles shows a clear increasein surface area with increasing number of PAAm-nanodiamond bilayers.With an increase in number of nanodiamond layers, the structure becomesmore porous. The average pore size of the core shell particlescontaining 9 layers of nanodiamond particles was also determined to be134 Å by the BET method.

As a characterization tool, the SPE capacity of the core-shell compositeparticles was also determined. FIG. 8C shows a plot of the capacity ofthe core-shell particles vs. the number of nanodiamond layers. Thecapacity increases substantially with an increase in the surface areafor core-shell composite particles containing greater than 5 or greaterthan 10 layers of nanodiamond particles, ca. 80-fold increase incapacity was observed 9 layers compared to solid non-porous cross-linkeddiamond powder.

The Examples demonstrate the effect of layer-by-layer deposition ofnanodiamond particles on various parameters, i.e., surface area,capacity, IR adsorption, etc., was determined. Core-shell diamondparticles have a higher surface area and capacity than solid diamondparticles, which increases with the number of PAAm-nanodiamond bilayers.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments are contemplated. The various aspects andembodiments disclosed herein are for purposes of illustration and arenot intended to be limiting. Additionally, the words “including,”“having,” and variants thereof (e.g., “includes” and “has”) as usedherein, including the claims, shall have the same meaning as the word“comprising” and variants thereof (e.g., “comprise” and “comprises”).

1. A method for manufacturing a porous composite particulate material,comprising: providing a plurality of acid-base-resistant core particlesand a plurality of acid-base-resistant shell particles; coating at leasta portion of the plurality of acid-base-resistant core particles, atleast a portion of the plurality of acid-base-resistant shell particles,or combinations thereof with polymer material; and adhering a portion ofthe plurality of acid-base-resistant shell particles to each of theplurality of acid-base-resistant core particles with the polymermaterial to form a plurality of composite particles.
 2. The method as inclaim 1, wherein the portion of the plurality of acid-base-resistantshell particles of each composite particle forms a plurality of porousshell layers, with each porous shell layer being formed in a separateadhering step.
 3. The method as in claim 1, wherein at least a portionof the plurality of acid-base-resistant shell particles comprises atleast one member selected from the group consisting of diamond,graphitic carbon, silicon carbide, boron nitride, tungsten carbide, andcombinations thereof.
 4. The method as in claim 1, wherein the pluralityof composite particles exhibits a particle size of at least about 1 μmand a surface area of at least about 5.0 m²/g.
 5. The method as in claim1, wherein the plurality of acid-base-resistant core particles exhibitsa particle size of at least an order of magnitude larger than theplurality of acid-base-resistant shell particles.
 6. The method as inclaim 1, wherein the polymer material is coated on the at least aportion of the plurality of acid-base-resistant shell particles beforethe act of adhering.
 7. The method as in claim 1, wherein the polymermaterial is coated on the at least a portion of the plurality ofacid-base-resistant core particles before the act of adhering.
 8. Themethod as in claim 1, wherein the acts of coating and adhering comprise:immersing the plurality of acid-base-resistant core particles in apolymer solution to form polymer-functionalized core particles;immersing the polymer-functionalized core particles in a suspension of afirst portion of the plurality of shell particles to yield a pluralityof intermediate composite particles; immersing the intermediatecomposite particles in a polymer solution to yieldpolymer-functionalized intermediate composite particles; and immersingthe polymer-functionalized intermediate composite particles in a secondportion of the plurality of acid-base-resistant shell particles to yieldcomposite particles having a plurality of layers of shell particles. 9.The method as in claim 1, further comprising bonding the plurality ofcomposite particles together.
 10. The method as in claim 8, wherein theplurality of acid-base-resistant shell particles comprise nanodiamondparticles with a particle size of less than about 1 μm.
 11. The methodas in claim 8, wherein the polymer solution comprises an amine polymer.12. The method as in claim 1, wherein the acts of coating and adheringcomprise: forming a bed of the plurality of acid-base-resistant coreparticles in a vessel; flowing a liquid polymeric material through thebed to coat the plurality of acid-base-resistant core particles thereofwith the polymer material; and flowing the plurality ofacid-base-resistant shell particles through the bed to adhere theportion of the plurality of acid-base-resistant shell particles to theeach of the plurality of acid-base-resistant core particles.
 13. Themethod as in claim 1, further comprising at least one of curing orcross-linking the polymer material after the act of adhering.
 14. Aporous composite particulate material, comprising: a plurality ofcomposite particles, each composite particle including, anacid-base-resistant core particle; a plurality of acid-base-resistantshell particles; and a polymeric layer bonding the plurality of shellparticles to the acid-base-resistant core particle.
 15. The porouscomposite particulate material as in claim 14, wherein the plurality ofacid-base-resistant shell particles form a plurality of porous shelllayers on the acid-base-resistant core particle, with each porous shelllayer being bonded to an adjacent porous shell layer by a layer ofpolymer.
 16. The porous composite particulate material as in claim 14,wherein at least a portion of the plurality of acid-base-resistant shellparticles comprises at least one member selected from the groupconsisting of diamond, graphitic carbon, tungsten carbide, boronnitride, and combinations thereof.
 17. The porous composite particulatematerial as in claim 14, wherein the plurality of composite particlesexhibits a particle size in a range from about 1 μm to about 10 μm and asurface area of at least about 25 m²/g.
 18. The porous compositeparticulate material as in claim 14, wherein the plurality of compositeparticles exhibits a particle size in a range from about 10 μm to about150 μm and a surface area of at least about 10 m²/g.
 19. The porouscomposite particulate material as in claim 14, wherein the plurality ofacid-base-resistant shell particles exhibits a particle size in a rangefrom about 1 nm to about 1000 nm.
 20. The porous composite particulatematerial as in claim 19, wherein the plurality of acid-base-resistantcore particles exhibits a particle size in a range from about 1 μm toabout 500 μm.
 21. The porous composite particulate material as in claim14, further comprising a layer of anionic polymer coated on at least aportion of the plurality of acid-base-resistant shell particles.
 22. Theporous composite particulate material as in claim 14, wherein thepolymeric layer comprises at least one amine polymer.
 23. The porouscomposite particulate material as in claim 14, wherein the polymericlayer is at least partially cross-linked.
 24. The porous compositeparticulate material as in claim 14, wherein the plurality of compositeparticles are bonded together.
 25. The porous composite particulatematerial as in claim 14, wherein the plurality of composite particles isin powder form.
 26. A method for using a porous composite particulatematerial, comprising: placing a porous composite particulate material ina vessel, the porous composite particulate material including, aplurality of composite particles, each composite particle including, anacid-base-resistant core particle; a plurality of acid-base-resistantshell particles; and a polymeric layer bonding of the plurality of shellparticles to the acid-base-resistant core particle; providing a mobilephase including at least two different components to be separated;flowing the mobile phase through the porous composite particulatematerial to physically separate the at least two different components;and recovering at least one of the two different components that havebeen separated.
 27. The method as in claim 26, further comprisingcleaning the porous composite particulate material by flowing a cleaningsolvent through the particle bed.
 28. The method as in claim 27, whereinat least one of the cleaning solvent or the mobile phase has a pHgreater than about
 10. 29. The method as in claim 27, wherein at leastone of the cleaning solvent or the mobile phase has a pH less than about2.
 30. A separation apparatus, comprising: a vessel having an inlet andan outlet; and a porous composite particulate material disposed withinthe vessel, the porous composite particulate material including, aplurality of composite particles, each composite particle including, anacid-base-resistant core particle; a plurality of acid-base-resistantshell particles; and a polymeric layer bonding of the plurality of shellparticles to the acid-base-resistant core particle.
 31. The separationapparatus as in claim 29, wherein the vessel is configured as achromatography column.